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Q99741 (CDC6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cell division control protein 6 homolog
Alternative name(s):
CDC6-related protein
Cdc18-related protein
Short name=HsCdc18
p62(cdc6)
Short name=HsCDC6
Gene names
Name:CDC6
Synonyms:CDC18L
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length560 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated.

Subunit structure

Interacts with PCNA, ORC1L, cyclin-CDK and HUWE1. Ref.2 Ref.5

Subcellular location

Nucleus. Cytoplasm. Note: The protein is nuclear in G1 and cytoplasmic in S-phase cells. Ref.2

Involvement in disease

Meier-Gorlin syndrome 5 (MGORS5) [MIM:613805]: A syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

Belongs to the CDC6/cdc18 family.

Ontologies

Keywords
   Biological processCell cycle
Cell division
DNA replication
Mitosis
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Dwarfism
   LigandATP-binding
Nucleotide-binding
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA replication

Traceable author statement. Source: Reactome

DNA replication checkpoint

Traceable author statement Ref.2. Source: ProtInc

G1/S transition of mitotic cell cycle

Traceable author statement. Source: Reactome

mitosis

Inferred from electronic annotation. Source: UniProtKB-KW

mitotic cell cycle

Traceable author statement. Source: Reactome

negative regulation of DNA replication

Traceable author statement Ref.2. Source: ProtInc

negative regulation of cell proliferation

Traceable author statement Ref.2. Source: ProtInc

positive regulation of chromosome segregation

Inferred from direct assay PubMed 21041660. Source: BHF-UCL

positive regulation of cytokinesis

Inferred from mutant phenotype PubMed 21041660. Source: BHF-UCL

regulation of cyclin-dependent protein serine/threonine kinase activity

Traceable author statement Ref.2. Source: ProtInc

regulation of mitotic metaphase/anaphase transition

Inferred from mutant phenotype PubMed 21041660. Source: BHF-UCL

regulation of transcription involved in G1/S transition of mitotic cell cycle

Traceable author statement. Source: Reactome

traversing start control point of mitotic cell cycle

Traceable author statement Ref.2. Source: ProtInc

   Cellular_componentGolgi apparatus

Inferred from direct assay. Source: HPA

cytoplasm

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 21041660. Source: BHF-UCL

spindle midzone

Inferred from direct assay PubMed 21041660. Source: BHF-UCL

spindle pole

Inferred from direct assay PubMed 21041660. Source: BHF-UCL

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

chromatin binding

Inferred from electronic annotation. Source: Ensembl

kinase binding

Inferred from physical interaction PubMed 21041660. Source: BHF-UCL

nucleoside-triphosphatase activity

Inferred from electronic annotation. Source: InterPro

nucleotide binding

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 560560Cell division control protein 6 homolog
PRO_0000150979

Regions

Nucleotide binding202 – 2098ATP Potential

Amino acid modifications

Modified residue451Phosphoserine Ref.7
Modified residue541Phosphoserine Ref.8
Modified residue1271Phosphoserine Ref.8

Natural variations

Natural variant2381T → A. Ref.3
Corresponds to variant rs4135010 [ dbSNP | Ensembl ].
VAR_019349
Natural variant2951D → N. Ref.3
Corresponds to variant rs4135012 [ dbSNP | Ensembl ].
VAR_019350
Natural variant2991T → M. Ref.3
Corresponds to variant rs4135013 [ dbSNP | Ensembl ].
VAR_019351
Natural variant3231T → R in MGORS5. Ref.10
VAR_065493
Natural variant3781R → H. Ref.3
Corresponds to variant rs4135016 [ dbSNP | Ensembl ].
VAR_019352
Natural variant4411V → I. Ref.3 Ref.4
Corresponds to variant rs13706 [ dbSNP | Ensembl ].
VAR_019353

Sequences

Sequence LengthMass (Da)Tools
Q99741 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 3ED7DE4AF80CB017

FASTA56062,720
        10         20         30         40         50         60 
MPQTRSQAQA TISFPKRKLS RALNKAKNSS DAKLEPTNVQ TVTCSPRVKA LPLSPRKRLG 

        70         80         90        100        110        120 
DDNLCNTPHL PPCSPPKQGK KENGPPHSHT LKGRRLVFDN QLTIKSPSKR ELAKVHQNKI 

       130        140        150        160        170        180 
LSSVRKSQEI TTNSEQRCPL KKESACVRLF KQEGTCYQQA KLVLNTAVPD RLPAREREMD 

       190        200        210        220        230        240 
VIRNFLREHI CGKKAGSLYL SGAPGTGKTA CLSRILQDLK KELKGFKTIM LNCMSLRTAQ 

       250        260        270        280        290        300 
AVFPAIAQEI CQEEVSRPAG KDMMRKLEKH MTAEKGPMIV LVLDEMDQLD SKGQDVLYTL 

       310        320        330        340        350        360 
FEWPWLSNSH LVLIGIANTL DLTDRILPRL QAREKCKPQL LNFPPYTRNQ IVTILQDRLN 

       370        380        390        400        410        420 
QVSRDQVLDN AAVQFCARKV SAVSGDVRKA LDVCRRAIEI VESDVKSQTI LKPLSECKSP 

       430        440        450        460        470        480 
SEPLIPKRVG LIHISQVISE VDGNRMTLSQ EGAQDSFPLQ QKILVCSLML LIRQLKIKEV 

       490        500        510        520        530        540 
TLGKLYEAYS KVCRKQQVAA VDQSECLSLS GLLEARGILG LKRNKETRLT KVFFKIEEKE 

       550        560 
IEHALKDKAL IGNILATGLP 

« Hide

References

« Hide 'large scale' references
[1]"A human protein related to yeast Cdc6p."
Williams R.S., Shohet R.V., Stillman B.
Proc. Natl. Acad. Sci. U.S.A. 94:142-147(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase."
Saha P., Chen J., Thome K.C., Lawlis S.J., Hou Z.H., Hendricks M., Parvin J.D., Dutta A.
Mol. Cell. Biol. 18:2758-2767(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, INTERACTION WITH PCNA; ORC1 AND CYCLIN-CDK.
[3]NIEHS SNPs program
Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-238; ASN-295; MET-299; HIS-378 AND ILE-441.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-441.
Tissue: Brain.
[5]"Cdc6 stability is regulated by the Huwe1 ubiquitin ligase after DNA damage."
Hall J.R., Kow E., Nevis K.R., Lu C.K., Luce K.S., Zhong Q., Cook J.G.
Mol. Biol. Cell 18:3340-3350(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUWE1.
[6]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54 AND SER-127, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Mutations in the pre-replication complex cause Meier-Gorlin syndrome."
Bicknell L.S., Bongers E.M., Leitch A., Brown S., Schoots J., Harley M.E., Aftimos S., Al-Aama J.Y., Bober M., Brown P.A., van Bokhoven H., Dean J., Edrees A.Y., Feingold M., Fryer A., Hoefsloot L.H., Kau N., Knoers N.V. expand/collapse author list , Mackenzie J., Opitz J.M., Sarda P., Ross A., Temple I.K., Toutain A., Wise C.A., Wright M., Jackson A.P.
Nat. Genet. 43:356-359(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MGORS5 ARG-323.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U77949 mRNA. Translation: AAB38317.1.
AF022109 mRNA. Translation: AAC52071.1.
AY150310 Genomic DNA. Translation: AAN10296.1.
BC025232 mRNA. Translation: AAH25232.1.
RefSeqNP_001245.1. NM_001254.3.
UniGeneHs.405958.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CCHX-ray1.70E/F89-100[»]
2CCIX-ray2.70F/I74-100[»]
4I5LX-ray2.43B/E70-90[»]
4I5NX-ray2.80B/E70-90[»]
ProteinModelPortalQ99741.
SMRQ99741. Positions 161-555.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107426. 42 interactions.
DIPDIP-28154N.
IntActQ99741. 21 interactions.
MINTMINT-1201847.
STRING9606.ENSP00000209728.

Chemistry

ChEMBLCHEMBL2311228.

PTM databases

PhosphoSiteQ99741.

Polymorphism databases

DMDM50400620.

Proteomic databases

PaxDbQ99741.
PRIDEQ99741.

Protocols and materials databases

DNASU990.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000209728; ENSP00000209728; ENSG00000094804.
GeneID990.
KEGGhsa:990.
UCSCuc002huj.1. human.

Organism-specific databases

CTD990.
GeneCardsGC17P038443.
HGNCHGNC:1744. CDC6.
HPAHPA050114.
HPA054703.
MIM602627. gene.
613805. phenotype.
neXtProtNX_Q99741.
Orphanet2554. Ear-patella-short stature syndrome.
PharmGKBPA26271.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1474.
HOGENOMHOG000045316.
HOVERGENHBG050860.
InParanoidQ99741.
KOK02213.
OMATPHLPPC.
OrthoDBEOG7QG44J.
PhylomeDBQ99741.
TreeFamTF101051.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.
REACT_383. DNA Replication.
SignaLinkQ99741.

Gene expression databases

ArrayExpressQ99741.
BgeeQ99741.
CleanExHS_CDC6.
GenevestigatorQ99741.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
3.40.50.300. 1 hit.
InterProIPR003593. AAA+_ATPase.
IPR015163. Cdc6_C_dom.
IPR016314. Cell_div_Cdc6/18.
IPR027417. P-loop_NTPase.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF09079. Cdc6_C. 1 hit.
[Graphical view]
PIRSFPIRSF001767. Cdc6. 1 hit.
SMARTSM00382. AAA. 1 hit.
SM01074. Cdc6_C. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ99741.
GeneWikiCDC6.
GenomeRNAi990.
NextBio4156.
PMAP-CutDBQ99741.
PROQ99741.
SOURCESearch...

Entry information

Entry nameCDC6_HUMAN
AccessionPrimary (citable) accession number: Q99741
Secondary accession number(s): Q8TB30
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: May 1, 1997
Last modified: April 16, 2014
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM